Inhaled nitric oxide (iNO) therapy has proven to be a safe and effective treatment for term newborns with PPHN and hypoxemic respiratory failure. Recent studies have focused on the potential role of iNO in the prevention of bronchopulmonary dysplasia (BPD), however, its effect on the pulmonary circulation in premature newborns has received less attention. Premature infants are particularly susceptible to the adverse effects of oxygen toxicity and lung inflammation which cause pulmonary parenchymal, airway, and pulmonary vascular injury, all of which contribute to the development of BPD and pulmonary hypertension. BPD remains a major cause of morbidity and mortality in premature newborns, and is characterized by chronic structural and functional pulmonary vascular abnormalities. Clinical trials of iNO in intubated premature newborns with hypoxemic respiratory failure have yielded conflicting results to date. Our multicenter trial of iNO in premature newborns (N=793) is near completion and will help clarify the role of iNO in this population of infants who require mechanical ventilation for hypoxemic respiratory failure, however, neonatologists are increasingly avoiding routine intubation and mechanical ventilation for even the most premature infants, opting instead to employ early, non-invasive continuous positive airway pressure (early CPAP, eCPAP) with the expectation that this mode of respiratory support will reduce acute lung injury and BPD. Unfortunately, preliminary observations have not demonstrated that this approach markedly reduces the development of BPD. Although eCPAP reduces the risk from VILI, it may not modify the injury caused by oxygen toxicity and lung inflammation in the immature lung. We hypothesize that low-dose iNO delivered non-invasively during eCPAP will reduce the incidence of BPD in premature newborns who do not require mechanical ventilation in the first 24 hours of life, and will reduce the early and late findings of pulmonary hypertension that characterize BPD. To test this hypothesis, we have designed a single-center randomized, controlled, masked pilot trial of non-invasive iNO treatment. Specific aims of this study are: 1)to determine if iNO reduces the combined endpoint of BPD/mortality in premature newborns (500-1250 grams birth weight) who do not require intubation in the first 24 hours of life; and 2) to determine if non-invasive iNO treatment decreases early and late pulmonary vascular abnormalities in this population.